The Pacific Northwest Prostate Cancer SPORE is a coordinated effort of four institutions with strong programs in prostate cancer research and career development: 1) the Fred Hutchinson Cancer Research Center (FHCRC); 2) the University of Washington (UW) and its affiliated institutions; 3) the Institute for Systems Biology (ISB); and 4) the University of British Columbia and the Prostate Center & Institute of Vancouver General Hospital. These three Seattle-based and the British Columbia (BC)-based institutions have a large number of investigators and laboratories dedicated to prostate cancer (CAP) research. Within this milieu, there already exists substantial technical infrastructure (e.g., genomics), strong multidisciplinary expertise (e.g., molecular biology, biochemistry, epidemiology, genetics, medical & radiation oncology, urology), and extensive resources (e.g., serum, DNA & tissue banks, CaP animal model facilities, CaP genomic arrays, and a CaP clinical trials organization). All four institutions have, and are in the process of generating, increasing resources for programs in translational CaP research and are committed to contributing significant resources toward the goals of this SPORE. The purpose of the SPORE is not only to perform the research projects proposed, but in a larger sense to form the "central supporting piece" to a large developing "mosaic" of coordinated translational CaP research in the Pacific Northwest. We believe the projects to be innovative and translational. Project 1 is a population-based study evaluating specific genetic polymorphisms in relation to CaP progression/mortality. Project 2 aims to characterize molecular alterations (karyotype, transcript) of disseminated CaP cells in the context of influencing the clinical management of patients as diagnostic and prognostic indicators. Project 3 will identify critical determinants of the transition from androgen-dependent to androgen-independent CaP, and will validate these findings in well-characterized pre-clinical models and clinical trials. Project 4 seeks to expand our already extensive work on the genomics of CaP and will determine if tumor gene expression profiles can predict the course of disease and response to cytotoxic chemotherapy. We have proposed five Cores in support of these projects (Administration, Specimen/Tissue, Biostatistics, Informatics & Gene Expression, and Clinical Research). The Career Development and Pilot Project Programs we propose will significantly embellish and strengthen the translational orientation of our prostate cancer research and expand opportunities for new investigators.